• 2019-07
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  • 2020-03
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  • 2020-08
  • br Our previous report showed that chronic H pylori


    710 Our previous report showed that chronic H pylori significantly upon hydrogen peroxide or di-tert-butyl hy- 769
    711 droperoxide treatment, but was unaltered upon NAC treat- 770
    infection significantly increases CAPZA1 expression in
    712 ment (Figure 4C). These observations suggest that oxidative 771
    the gastric mucosa of Mongolian gerbils and that CAP-
    713 stress induces CAPZA1 expression via enhanced histone H3 772
    ZA1-overexpressing cells are detected throughout the
    714 acetylation of the CAPZA1 promoter.
    gastric mucosal epithelium from gastric glands to gastric
    715 H pylori infection signi cantly increased CAPZA1 774
    pits. 21 By contrast, H pylori infection does not up-regulate
    expression in the gastric mucosa of Mongolian gerbils 775
    CAPZA1 expression in AGS Ibrutinib in vitro, indicating that it
    717 (Figure 5A). Malondialdehyde and protein carbonyl levels 776
    not directly induce CAPZA1 expression in gastric
    are used as biomarkers of oxidative stress. There was a 777
    epithelial cells. 21 In the present study, we investigated how
    significant linear correlation between CAPZA1 expression 778
    CAPZA1 expression is induced in H pylori–infected gastric
    mucosal epithelium. The inflammatory response in H pylo-
    721 ri–infected gastric mucosa, which is induced via reactive CAPZA1 expression and protein carbonylation (r ¼ 0.65; 780
    722 oxygen species and reactive nitrogen species generated by P ¼ .04) (Figure 5B). To visually assess the relationship 781
    723 neutrophils and monocytes, contributes to the development between oxidative stress and CAPZA1 overexpression in H 782
    724 pylori–infected gastric epithelium, we performed immuno- 783
    of H pylori–related disease. 28 On the other hand, CD44v9-
    staining of 8-hydroxy-2’-deoxyguanosine, which is produced 784
    positive cells show enhanced resistance to reactive oxygen
    726 upon oxidative damage of the nucleoside deoxyguanosine 785
    species owing to stabilization of the glutamate-cystine
    727Q12 and then excreted extracellularly. CAPZA1-overexpressing 786
    transporter xCT at the cytoplasmic membrane.3 Ishimoto
    728 et al 29 proposed that chronic inflammation induced by H cells in H pylori–infected gastric mucosa mainly co- 787
    localized with 8-hydroxy-2’-deoxyguanosine–positive cells 788
    pylori infection leads to the generation of CD44v9-positive
    cells. We thus hypothesized that this inflammatory
    731 stress induced by H pylori infection increases CAPZA1 790
    response contributes to the induction of CAPZA1 expres-
    732 expression. We subsequently examined whether CD44v9 791
    sion, leading to development of CD44v9-positive cells. To
    733 expression was induced in CAPZA1-overexpressing cells in 792
    investigate this, we examined changes in CAPZA1 expres-
    734 H pylori–infected gastric mucosa. In gastric mucosa of 2 of 5 793
    sion in AGS cells upon treatment with hydrogen peroxide or
    735 Mongolian gerbils, CD44v9-positive cells were detected 794
    di-tert-butyl peroxide. Treatment with hydrogen peroxide
    736 among CAPZA1-overexpressing cells, indicating that 795
    or di-tert-butyl peroxide increased CAPZA1 expression in a
    dose-dependent manner (Figure 4A). In addition, these in-
    738 expression (Figure 6). When considered together with the 797
    creases were abrogated by N-acetylcysteine (NAC) treat-
    739 in vitro H pylori infection data, adherence of H pylori to 798
    ment (Figure 4B). We previously reported that alteration in
    740 CAPZA1-overexpressing cells leading to CagA accumulation 799
    the chromatin structure by acetylated histone H3 is involved
    741 in H pylori–infected gastric mucosa is considered to be 800
    in induction of CAPZA1
    21 We subsequently
    742 expression. required for the development of CD44v9-positive cells.
    analyzed alterations in the
    chromatin structure of the
    We subsequently investigated the effect of eradication 802
    CAPZA1 proximal promoter region in AGS cells treated with
    744 therapy on the level of CAPZA1 expression by examining 5 803
    hydrogen peroxide or di-tert-butyl peroxide by performing
    745 patients with H pylori infection and 5 patients who had 804
    chromatin immunoprecipitation (ChIP) with an antibody